Cellular mechanisms for dopamine D4 receptor-induced homeostatic regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors.

ABSTRACT: Aberrant dopamine D(4) receptor function has been implicated in mental illnesses, including schizophrenia and attention deficit-hyperactivity disorder. Recently we have found that D(4) receptor exerts an activity-dependent bi-directional regulation of AMPA receptor (AMPAR)-mediated synaptic currents in pyramidal neurons of prefrontal cortex (PFC) via the dual control of calcium/calmodulin kinase II (CaMKII) activity. In this study, we examined the signaling mechanisms downstream of CaMKII that govern the complex effects of D(4) on glutamatergic transmission. We found that in PFC neurons at high activity state, D(4) suppresses AMPAR responses by disrupting the kinesin motor-based transport of GluR2 along microtubules, which was accompanied by the D(4) reduction of microtubule stability via

SUBMITTER: Yuen EY 

PROVIDER: S-EPMC3137069 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature